Abstract
Objective:
To determine if resistance to weight gain is associated with alterations in sleep–wake states and orexin receptor gene expression.
Design:
Three-month-old obesity-susceptible Sprague–Dawley (SD) and obesity-resistant (OR) rats were fed standard rodent chow. Sleep–wake cycle was measured by radiotelemetry and orexin receptor profiles in sleep–wake regulatory areas of the brain were quantified by quantitative reverse transcriptase-PCR.
Subjects:
Adult male obesity-susceptible SD and selectively bred OR rats.
Measurements:
Body weight, food intake, energy efficiency, percent time spent in active wake (AW), quiet wake (QW), slow-wave sleep (SWS), rapid eye movement (REM) sleep, number and mean duration of sleep–wake episodes, number of stage transitions, SWS sleep delta power and orexin receptor mRNA levels were measured.
Results:
OR rats weighed significantly less and had lower energy efficiency than SD rats. Food intake was not different between SD and OR rats. Time spent in QW was similar between groups, and therefore AW and QW were combined and are referred to as ‘wakefulness’. OR rats spent significantly more time in wakefulness and less time in SWS compared with SD rats during the 24-h recording period. Relative to SD rats, OR rats had significantly fewer sleep–wake episodes and the duration of the episodes were prolonged, indicating less fragmented sleep. Furthermore, OR rats had fewer transitions between sleep stages, which indicates that OR rats were behaviorally more stable and had more consolidated sleep than obesity-susceptible SD rats. OR rats showed lower delta power during SWS, indicating a lower sleep drive. Our results showed greater orexin receptor gene expression in sleep regulatory brain areas in OR rats.
Conclusion:
These results show that prolonged wakefulness, better sleep quality, lower sleep drive and greater orexin signaling may confer protection against obesity.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Knutson KL, Van Cauter E . Associations between sleep loss and increased risk of obesity and diabetes. Ann NY Acad Sci 2008; 1129: 287–304.
Wolk R, Shamsuzzaman AS, Somers VK . Obesity, sleep apnea, and hypertension. Hypertension 2003; 42: 1067–1074.
Dixon JB, Dixon ME, Anderson ML, Schachter L, O’brien PE . Daytime sleepiness in the obese: not as simple as obstructive sleep apnea. Obesity (Silver Spring) 2007; 15: 2504–2511.
Gangwisch J, Heymsfield S . Sleep deprivation as a risk factor for obesity: results based on the NHANES I. Sleep 2005; 28: 1289–1296.
Patel SR, Hu FB . Short sleep duration and weight gain: a systematic review. Obesity (Silver Spring) 2008; 16: 643–653.
Jennings JR, Muldoon MF, Hall M, Buysse DJ, Manuck SB . Self-reported sleep quality is associated with the metabolic syndrome. Sleep 2007; 30: 219–223.
Guan Z, Vgontzas AN, Bixler EO, Fang J . Sleep is increased by weight gain and decreased by weight loss in mice. Sleep 2008; 31: 627–633.
Vgontzas AN, Bixler EO, Chrousos GP, Pejovic S . Obesity and sleep disturbances: meaningful sub-typing of obesity. Arch Physiol Biochem 2008; 114: 224–236.
Jenkins JB, Omori T, Guan Z, Vgontzas AN, Bixler EO, Fang J . Sleep is increased in mice with obesity induced by high-fat food. Physiol Behav 2006; 87: 255–262.
Laposky AD, Shelton J, Bass J, Dugovic C, Perrino N, Turek FW . Altered sleep regulation in leptin-deficient mice. Am J Physiol Regul Integr Comp Physiol 2006; 290: R894–R903.
Megirian D, Dmochowski J, Farkas GA . Mechanism controlling sleep organization of the obese Zucker rats. J Appl Physiol 1998; 84: 253–256.
Danguir J . Sleep patterns in the genetically obese Zucker rat: effect of acarbose treatment. Am J Physiol 1989; 256: R281–R283.
Rao MN, Blackwell T, Redline S, Stefanick ML, Ancoli-Israel S, Stone KL . Association between sleep architecture and measures of body composition. Sleep 2009; 32: 483–490.
Liu X, Forbes EE, Ryan ND, Rofey D, Hannon TS, Dahl RE . Rapid eye movement sleep in relation to overweight in children and adolescents. Arch Gen Psychiatry 2008; 65: 924–932.
Kalra M, Mannaa M, Fitz K, Kumar S, Chakraborty R, Sheng X et al. Effect of surgical weight loss on sleep architecture in adolescents with severe obesity. Obes Surg 2008; 18: 675–679.
Van Cauter E, Knutson KL . Sleep and the epidemic of obesity in children and adults. Eur J Endocrinol 2008; 159 (Suppl 1): S59–S66.
Touchette E, Petit D, Tremblay RE, Boivin M, Falissard B, Genolini C et al. Associations between sleep duration patterns and overweight/obesity at age 6. Sleep 2008; 31: 1507–1514.
Marshall NS, Glozier N, Grunstein RR . Is sleep duration related to obesity? A critical review of the epidemiological evidence. Sleep Med Rev 2008; 12: 289–298.
Lauderdale DS, Knutson KL, Yan LL, Rathouz PJ, Hulley SB, Sidney S et al. Objectively measured sleep characteristics among early-middle-aged adults: the CARDIA study. Am J Epidemiol 2006; 164: 5–16.
Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med 2005; 165: 863–867.
Taheri S, Lin L, Austin D, Young T, Mignot E . Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 2004; 1: 210–217.
Spiegel K, Leproult R, Van Cauter E . Impact of sleep debt on metabolic and endocrine function. Lancet 1999; 354: 1435–1439.
Dixon JB, O’Brien PE . Changes in comorbidities and improvements in quality of life after LAP-BAND placement. Am J Surg 2002; 184: 51S–54S.
Kwok EH, Dun NJ . Orexin/Hypocretin system: obesity, narcolepsy and beyond. Drug News Perspect 2002; 15: 166–174.
Laposky AD, Bradley MA, Williams DL, Bass J, Turek FW . Sleep-wake regulation is altered in leptin-resistant (db/db) genetically obese and diabetic mice. Am J Physiol Regul Integr Comp Physiol 2008; 295: R2059–R2066.
Baranowska B, Wolińska-Witort E, Martyńska L, Chmielowska M, Baranowska-Bik A . Plasma orexin A, orexin B, leptin, neuropeptide Y (NPY) and insulin in obese women. Neuro Endocrinol Lett 2005; 26: 293–296.
Bronský J, Nedvídková J, Zamrazilová H, Pechová M, Chada M, Kotaska K et al. Dynamic changes of orexin A and leptin in obese children during body weight reduction. Physiol Res 2007; 56: 89–96.
Stricker-Krongrad A, Richy S, Beck B . Orexins/hypocretins in the ob/ob mouse: hypothalamic gene expression, peptide content and metabolic effects. Regul Pept 2002; 104: 11–20.
Cai XJ, Evans ML, Lister CA, Leslie RA, Arch JR, Wilson S et al. Hypoglycemia activates orexin neurons and selectively increases hypothalamic orexin-B levels: responses inhibited by feeding and possibly mediated by the nucleus of the solitary tract. Diabetes 2001; 50: 105–112.
Adamantidis A, de Lecea L . The hypocretins as sensors for metabolism and arousal. J Physiol 2009; 587: 33–40.
Novak CM, Kotz CM, Levine JA . Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats. Am J Physiol Endocrinol Metab 2006; 290: E396–E403.
Ohno K, Sakurai T . Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front Neuroendocrinol 2008; 29: 70–87.
Kok SW, Meinders AE, Overeem S, Lammers GJ, Roelfsema F, Frolich M et al. Reduction of plasma leptin levels and loss of its circadian rhythmicity in hypocretin (orexin)-deficient narcoleptic humans. J Clin Endocrinol Metab 2002; 87: 805–809.
Mondal MS, Nakazato M, Matsukura S . Characterization of orexins (hypocretins) and melanin-concentrating hormone in genetically obese mice. Regul Pept 2002; 104: 21–25.
Taheri S, Gardiner J, Hafizi S, Murphy K, Dakin C, Seal L et al. Orexin A immunoreactivity and preproorexin mRNA in the brain of Zucker and WKY rats. Neuroreport 2001; 12: 459–464.
Levin BE, Hogan S, Sullivan AC . Initiation and perpetuation of obesity and obesity resistance in rats. Am J Physiol 1989; 256: R766–R771.
Teske JA, Levine AS, Kuskowski M, Levine JA, Kotz CM . Elevated hypothalamic orexin signaling, sensitivity to orexin A, and spontaneous physical activity in obesity-resistant rats. Am J Physiol Regul Integr Comp Physiol 2006; 291: R889–R899.
Kotz CM, Teske JA, Billington CJ . Neuroregulation of nonexercise activity thermogenesis and obesity resistance. Am J Physiol Regul Integr Comp Physiol 2008; 294: R699–R710.
Teske JA, Billington CJ, Kotz CM . Neuropeptidergic mediators of spontaneous physical activity and non-exercise activity thermogenesis. Neuroendocrinology 2008; 87: 71–90.
Porkka-Heiskanen T, Alanko L, Kalinchuk A, Heiskanen S, Stenberg D . The effect of age on prepro-orexin gene expression and contents of orexin A and B in the rat brain. Neurobiol Aging 2004; 25: 231–238.
George O, Parducz A, Dupret D, Kharouby M, Le Moal M, Piazza P et al. Smad-dependent alterations of PPT cholinergic neurons as a pathophysiological mechanism of age-related sleep-dependent memory impairments. Neurobiol Aging 2006; 27: 1848–1858.
Zhang Y, Matheny M, Tümer N, Scarpace PJ . Aged-obese rats exhibit robust responses to a melanocortin agonist and antagonist despite leptin resistance. Neurobiol Aging 2004; 25: 1349–1360.
Dugovic C, Shelton JE, Aluisio LE, Fraser IC, Jiang X, Sutton SW et al. Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat. J Pharmacol Exp Ther 2009; 330: 142–151.
Mavanji V, Siwek DF, Patterson EH, Spoley EE, Datta S . Effects of passive-avoidance training on sleep-wake state-specific activity in the basolateral and central nuclei of the amygdala. Behav Neurosci 2003; 117: 751–759.
Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell TE . Behavioral state instability in orexin knock-out mice. J Neurosci 2004; 24: 6291–6300.
van den Berg JF, Knvistingh Neven A, Tulen JH, Hofman A, Witteman JC, Miedema HM et al. Actigraphic sleep duration and fragmentation are related to obesity in the elderly: the Rotterdam Study. Int J Obes (Lond) 2008; 32: 1083–1090.
Wells AS, Read NW, Fried M, Boroviska J, D’Amato M . Influences of fat and carbohydrate on postprandial sleepiness, mood, and hormones. Physiol Behav 1997; 61: 679–686.
Hansen MK, Kapás L, Fang J, Krueger JM . Cafeteria diet-induced sleep is blocked by subdiaphragmatic vagotomy in rats. Am J Physiol 1998; 274: R168–R174.
Brunner DP, Dijk DJ, Borbély AA . Repeated partial sleep deprivation progressively changes in EEG during sleep and wakefulness. Sleep 1993; 16: 100–113.
Greene R, Siegel J . Sleep: a functional enigma. Neuromolecular Med 2004; 5: 59–68.
Sakurai T . Roles of orexin/hypocretin in regulation of sleep/wakefulness and energy homeostasis. Sleep Med Rev 2005; 9: 231–241.
Smith MI, Piper DC, Duxon MS, Upton N . Evidence implicating a role for orexin-1 receptor modulation of paradoxical sleep in the rat. Neurosci Lett 2003; 341: 256–258.
John J, Wu MF, Siegel JM . Systemic administration of hypocretin-1 reduces cataplexy and normalizes sleep and waking durations in narcoleptic dogs. Sleep Res Online 2000; 3: 23–28.
Beuckmann CT, Sinton CM, Williams SC, Richardson JA, Hammer RE, Sakurai T et al. Expression of a poly-glutamine-ataxin-3 transgene in orexin neurons induces narcolepsy-cataplexy in the rat. J Neurosci 2004; 24: 4469–4477.
Chen L, Thakkar MM, Winston S, Bolortuya Y, Basheer R, McCarley RW . REM sleep changes in rats induced by siRNA-mediated orexin knockdown. Eur J Neurosci 2006; 24: 2039–2048.
Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med 2007; 13: 150–155.
Wu MF, John J, Maidment N, Lam HA, Siegel JM . Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement. Am J Physiol Regul Integr Comp Physiol 2002; 283: R1079–R1086.
Pedrazzoli M, D’Almeida V, Martins PJ, Machado RB, Ling L, Nishino S et al. Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation. Brain Res 2004; 995: 1–6.
Nuñez A, Moreno-Balandrán ME, Rodrigo-Angulo ML, Garzón M, De Andrés I . Relationship between the perifornical hypothalamic area and oral pontine reticular nucleus in the rat. Possible implication of the hypocretinergic projection in the control of rapid eye movement sleep. Eur J Neurosci 2006; 24: 2834–2842.
Carter ME, Borg JS, de Lecea L . The brain hypocretins and their receptors: mediators of allostatic arousal. Curr Opn Pharmacol 2009; 9: 39–45.
Methippara MM, Alam MN, Szymusiak R, McGinty D . Effects of lateral preoptic area aplication of orexin-A on sleep-wakefulness. Neuroreport 2000; 11: 3423–3426.
Krueger JM . The role of cytokines in sleep regulation. Curr Pharm Des 2008; 14: 3408–3416.
Fenton JI, Nuñez NP, Yakar S, Perkins SN, Hord NG, Hursting SD . Diet-induced adiposity alters the serum profile of inflammation in C57BL/6N mice as measured by antibody array. Diabetes Obes Metab 2009; 11: 343–354.
Pérez-Echarri N, Pérez-Matute P, Marcos-Gómez B, Baena MJ, Marti A, Martínez JA et al. Differential inflammatory status in rats susceptible or resistant to diet-induced obesity: effects of EPA ethyl ester treatment. Eur J Nutr 2008; 47: 380–386.
Novak CM, Levine JA . Daily intraparaventricular orexin-A treatment induces weight loss in rats. Obesity (Silver Spring) 2009; 17: 1493–1498.
Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM et al. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 2001; 30: 345–354.
Sakurai T, Izawa T, Kizaki T, Ogasawara JE, Shirato K, Imaizumi K et al. Exercise training decreases expression of inflammation-related adipokines through reduction of oxidative stress in rat white adipose tissue. Biochem Biophys Res Commun 2009; 379: 605–609.
Basta M, Lin HM, Pejovic S, Sarrigiannidis A, Bixler E, Vgontzas AN . Lack of regular exercise, depression, and degree of apnea are predictors of excessive daytime sleepiness in patients with sleep apnea: sex differences. J Clin Sleep Med 2008; 4: 19–25.
Blanco-Centurion CA, Shiromani PJ . Beneficial effects of regular exercise on sleep in old F344 rats. Neurobiol Aging 2006; 27: 1859–1869.
España RA, McCormack SL, Mochizuki T, Scammell TE . Running promotes wakefulness and increases cataplexy in orexin knockout mice. Sleep 2007; 30: 1417–1425.
Acknowledgements
Funding for this publication was provided by the Department of Veterans Affairs, Minnesota Department of Employment and Economic Development from the State's legislative appropriation for the Minnesota partnership for Biotechnology and Medical Genomics, and Minnesota Obesity Center Grant P30 DK050456 from the National Institute of Diabetes and Digestive and Kidney Diseases and a grant from the Obesity Society.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Mavanji, V., Teske, J., Billington, C. et al. Elevated sleep quality and orexin receptor mRNA in obesity-resistant rats. Int J Obes 34, 1576–1588 (2010). https://doi.org/10.1038/ijo.2010.93
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2010.93
Keywords
This article is cited by
-
Synchronous neuronal interactions in rat hypothalamic culture: a novel model for the study of network dynamics in metabolic disorders
Experimental Brain Research (2021)
-
Noise-induced sleep disruption increases weight gain and decreases energy metabolism in female rats
International Journal of Obesity (2019)
-
The effects of Jiao-Tai-Wan on sleep, inflammation and insulin resistance in obesity-resistant rats with chronic partial sleep deprivation
BMC Complementary and Alternative Medicine (2017)
-
Role of orexin-A in the ventrolateral preoptic area on components of total energy expenditure
International Journal of Obesity (2017)
-
Night time sleep macrostructure is altered in otherwise healthy 10-year-old overweight children
International Journal of Obesity (2014)